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Research – Guil ain Barre Syndrome
Research on Guillain Barre Syndrome & the different variants including Acute
Motor Sensory Axonal Neuropathy (AMSAN)
Brief
Detail on recovery including timeframes of each variant. For example, a
diagnosis of what period of time would be reasonable to consider if the
diagnosis is going to be or likely to be permanent.
Stats on cases where permanency is established.
Date
05/08/2021
Requester(s)
Jenni Gs47F - personal privacy
Researcher
Jane Ss47F - personal privacy
Cleared
N/A
Please note:
The research and literature reviews col ated by our TAB Research Team are not to be shared external to the Branch. These
are for internal TAB use only and are intended to assist our advisors with their reasonable and necessary decision-making.
Delegates have access to a wide variety of comprehensive guidance material. If Delegates require further information on
access or planning matters they are to call the TAPS line for advice.
The Research Team are unable to ensure that the information listed below provides an accurate & up-to-date snapshot of
these matters.
The contents of this document are OFFICIAL
1 Contents
2 Summary ......................................................................................................................................... 1
3 Overview ......................................................................................................................................... 2
4 Variants and Subtypes .................................................................................................................... 3
5 Clinical Course ................................................................................................................................. 4
6 Prognosis ......................................................................................................................................... 5
7 Long Term Outcomes ...................................................................................................................... 6
8 References ...................................................................................................................................... 9
2 Summary
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• Guillain–Barré syndrome has many variants and can be placed into subtypes using
electrophysiological/nerve conduction studies. However, the literature investigating
recovery and long term outcomes present results for the condition as a whole rather
than within these classifications.
• The prognosis of GBS is generally considered favourable with most recovery
occurring in the first 12 months.
• Patients have been shown to experience a range of long-term residual problems,
including incomplete recovery of motor and sensory function, as well as fatigue, pain
and psychological distress.
o These poor outcomes have been shown to be present up to 10 years after
the acute phase.
o One literature review found that GBS cause’s severe persistent disability in
14% of patients at 1 year.
o Other studies have shown that improvements can occur 2-5 years after
diagnosis, however, this does not mean they have completely recovered.
3 Overview
Guillain–Barré syndrome (GBS) is an inflammatory disease of the peripheral nervous system
(PNS) and is the most common cause of acute flaccid paralysis, with an annual global
incidence of approximately 1–2 per 100,000 person-years [1]. GBS occurs more frequently in
males than in females and the incidence increases with age, although al age groups can be
affected [1].
Patients with GBS typical y present with weakness and sensory signs in the legs that
progress to the arms and cranial muscles. Clinical presentation of the disease is
heterogeneous and the diagnosis of GBS is based on the patient history and neurological,
electrophysiological and cerebrospinal fluid (CSF) examinations.
In lower resource countries where Electrophysiological studies are not available, the
Brighton Criteria is utilised to make a diagnosis. The table below is used to rank level of
severity [2].
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4 Variants and Subtypes
Clinical variants of GBS exist, with some patients having a distinct and persistent clinical
variant of GBS that does not progress to the classic pattern of sensory loss and weakness
[3]. These variants include [3]:
• Classic Sensorimotor GBS:
o Rapidly progressive symmetrical weakness and sensory signs with absent or
reduced tendon reflexes, usual y reaching nadir within 2 weeks
o 30-85% of cases
• Pure motor
o Motor weakness without sensory signs
o 5-70% of cases
• Paraparetic
o Paresis restricted to the legs
o 5-10%
• Pharyngeal–cervical– brachial
o Bilateral facial weakness, paraesthesias and reduced reflexes
• Bilateral facial palsy with paraesthesias
o Bilateral facial weakness, paraesthesias and reduced reflexes
o <5%
• Pure Sensory
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o Acute or subacute sensory neuropathy without other deficits
o <1%
• Miller Fisher syndrome
o Ophthalmoplegia, ataxia and areflexia. Incomplete forms with isolated ataxia
(acute ataxic neuropathy) or ophthalmoplegia (acute ophthalmoplegia) can
occur. Overlaps with classical sensorimotor GBS in an estimated 15% of
patients.
o 5-25% of cases
o Weakness limited to the cranial nerves (bilateral facial palsy with
paraesthesias)
• Bickerstaff brainstem encephalitis
o Ophthalmoplegia, ataxia, areflexia, pyramidal tract signs and impaired
consciousness, often overlapping with sensorimotor GBS.
o <5% of cases
In general, GBS variants are rarely ‘pure’ and often overlap in part with the classic syndrome
or show features that are typical of other variant forms.
Electrophysiological/nerve conduction studies provide evidence of PNS dysfunction and can
distinguish between the subtypes of GBS, however, these tests are not required to make a
clinical diagnosis of GBS and should not delay treatment [3, 4]. Subtypes include:
•
Acute inflammatory demyelinating polyradiculoneuropathy (AIDP)
o Characterized by progressive areflexic (muscles don’t respond to stimuli)
weakness and mild sensory changes. Sensory symptoms often precede motor
weakness. AIDP is the most common form of GBS in North America and
Europe
•
Acute motor axonal neuropathy (AMAN)
o Key clinical features of pure motor weakness, areflexia, absence of sensory
symptoms, and lack of neurophysiologic evidence of demyelination.
•
Acute motor sensory axonal neuropathy (AMSAN) [5]
o Characterised by acute onset of distal weakness, loss of deep tendon reflexes
and sensory symptoms
o Electrophysiological studies show mildly reduced nerve conduction velocities
combined with a marked reduction of muscle action and sensory nerve action
potentials.
5 Clinical Course
Disease progression can be rapid, and most patients with GBS reach their maximum
disability within 2 weeks. About 20% of patients with GBS develop respiratory failure and
require mechanical ventilation. Cardiac arrhythmias and blood pressure instability can occur
owing to involvement of the autonomic nervous system [6]. This involvement of the
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autonomic nervous system contributes to mortality, which is estimated at 3–10% for
patients with GBS even with the best medical care available [6, 7].
After the initial progressive phase, patients with GBS reach a plateau phase that can last
from days to weeks or months, after which they start to recover, and 60–80% of patients
with GBS are able to walk independently 6 months after disease onset, with or without
treatment [8, 9]. GBS is a monophasic illness (a disorder that causes only one episode of
inflammation in the central nervous system), although some patients can deteriorate after
first stabilizing or improving on therapy — a phenomenon that is referred to as a treatment-
related fluctuation (TRF). Relapses of GBS can occur in 2–5% of patients [8, 10, 11]. Willison,
Jacobs [6] have developed a figure (below) which describes the clinical course of the
disease.
6 Prognosis
The
prognosis of GBS is general y considered favourable. Despite the demonstrated
efficacy of plasma exchange (PE) and intravenous immunoglobulins (IVIg), GBS however
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remains a disabling disease in a significant proportion of patients, and these treatments
have not improved mortality which ranges between 3-7% depending on the country [6, 7].
The clinical course and long term outcome of the disease is highly variable and early
recognition of patients with poor outcome is needed to personalise and improve treatment.
Prognostic models do not exist (for variants or subtypes), however, development of these
could help to identify patients who need additional treatment and monitoring.
Patient characteristics consistently related to poor prognostic outcome in GBS are [6, 12]:
• High age (aged 40 years and over)
• Preceding diarrhoea (or C jejuni infection in the past 4 weeks)
• Greater disability/weaker muscles at admission
• Short interval between symptom onset and admission
• Mechanical ventilation
• Absent/ low amplitude compound muscle action potentials
The modified Erasmus GBS outcome score (mEGOS), which is based on these clinical
characteristics, can be used 2 weeks after admission to predict the ability of the patient to
walk at 6 months [13]. The mEGOS requires the Medical Research Council (MRC) Scale for
Muscle Strength score instead of disability and can predict outcome as soon as 1 week after
admission, when therapeutic interventions are probably even more effective [3, 6]. The risk
of respiratory failure is associated with rate of disease progression, severity of limb
weakness, peroneal nerve conduction block, and low vital capacity. This risk can be
predicted for individual patients using Erasmus GBS Respiratory Insufficiency Score (EGRIS);
based on the severity of weakness (expressed as MRC sum score); onset of weakness; and
facial palsy, bulbar weakness, or both [14]. These models have not been validated for use in
children and patients with axonal forms of GBS.
7 Long Term Outcomes
The long-term follow-up system of patients with GBS is not wel established worldwide [15].
Many fol ow up studies only review patients 12 months after the acute state. Nonetheless,
long-term function has been shown to be compromised in a significant proportion of
subjects. Clinical improvement is usually most extensive in the first year after disease onset
and can continue for >5 years [3, 15, 16].
Patients with GBS have been shown to experience a range of long-term residual problems,
including incomplete recovery of motor and sensory function, as wel as fatigue, pain and
psychological distress [16-18].
A high quality literature review by Rajabally and Uncini [12] was conducted to determine
outcomes and predictors in adequately treated (with PE and IVIg), adult-onset GBS. The
table below shows the results from this review. Key findings include that GBS cause’s severe
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persistent disability in 14% of patients at 1 year and loss of full strength, persistent pain and
need for professional change occurs in about 40% of patients.
The first long-term study of residual health status was published in 1997 analysing a cohort
of 123 GBS patients fol owed up 3-6 years after their illness [19]. The authors found residual
altered psychosocial function in al GBS patient groups whether or not they had persistent
residual symptoms. However, the ‘physical sickness impact profile’ score correlated with the
GBS functional score [19].
The same group later showed long-term reduction in health-related quality of life despite
good physical recovery [20]. They also studied the effects on private life of GBS patients 3-6
years after the illness, with 31% showing moderate to serious physical residual symptoms
after a functional assessment [21]. Also, and importantly, employment change was needed
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in 38% of cases and leisure activities had altered in 52% after the illness. However, over 20%
of patients still noticed improvement 2.5-6.5 years after onset [21].
Long term outcomes in patients requiring mechanical ventilation has shown that 21% do not
regain independent ambulation [22]. This group has the highest mortality rate – which is
20%.
A 3 year fol ow up study to investigate the outcomes of 82 patients found that [23]:
• Poor functional outcome was found in 39% of patients at year 1 and 30% at year 3.
• Paresthesias/dysesthesias were detected in 60% of patients after 1 year and 43%
after 3 years.
• Musculoskeletal pain was present in 40% of patients at year 1 and 33% at year 3.
• Significant fatigue after 1 year was found in 21% of subjects and after 3 years in 7%.
The longest study to date (up to 10 years) included a small sample of 29 patients. Results
showed that at 10 years, the facial paralysis found in 5 participants at 2 years was still
present, 11 participants (38%) experienced paresthesia, 6 (21%) had limitations in their
arms, and 15 (52%) had limitations in walking [16].
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8 References
1.
Sejvar JJ, Baughman AL, Wise M, Morgan OW. Population Incidence of Guil ain-Barré
Syndrome: A Systematic Review and Meta-Analysis. Neuroepidemiology [Internet]. 2011; 36(2):[123-
33 pp.]. Available from: https://www.karger.com/DOI/10.1159/000324710.
2.
Ghazanfar H, Qazi R, Ghazanfar A, Iftekhar S. Significance of Brighton Criteria in the Early
Diagnosis and Management of Guil ain-Barré Syndrome. Cureus [Internet]. 2020; 12(5):[e8318-e
pp.]. Available from: https://pubmed.ncbi.nlm.nih.gov/32607301
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7320636/.
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Leonhard SE, Mandarakas MR, Gondim FAA, Bateman K, Ferreira MLB, Cornblath DR, et al.
Diagnosis and management of Guil ain–Barré syndrome in ten steps. Nature Reviews Neurology
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4.
Hadden RDM, Cornblath DR, Hughes RAC, Zielasek J, Hartung HP, Toyka KV, et al.
Electrophysiological classification of guillain-barré syndrome: Clinical associations and outcome.
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https://doi.org/10.1002/ana.410440512.
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Rostásy KM, Huppke P, Beckers B, Brockmann K, Degenhardt V, Wesche B, et al. Acute motor
and sensory axonal neuropathy (AMSAN) in a 15-year-old boy presenting with severe pain and distal
muscle weakness. Neuropediatrics [Internet]. 2005 Aug; 36(4):[260-4 pp.].
6.
Wil ison HJ, Jacobs BC, van Doorn PA. Guil ain-Barré syndrome. The Lancet [Internet]. 2016
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van den Berg B, Bunschoten C, van Doorn PA, Jacobs BC. Mortality in Guil ain-Barré
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Doets AY, Verboon C, van den Berg B, Harbo T, Cornblath DR, Wil ison HJ, et al. Regional
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https://doi.org/10.1093/brain/awy232.
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Ruts L, Drenthen J, Jacobs BC, van Doorn PA. Distinguishing acute-onset CIDP from
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http://n.neurology.org/content/74/21/1680.abstract.
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Kleyweg RP, van der Meché FG. Treatment related fluctuations in Guillain-Barré syndrome
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13.
van Koningsveld R, Steyerberg EW, Hughes RAC, Swan AV, van Doorn PA, Jacobs BC. A
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Walgaard C, Lingsma HF, Ruts L, Drenthen J, van Koningsveld R, Garssen MJP, et al.
Prediction of respiratory insufficiency in Guillain-Barré syndrome. Annals of Neurology [Internet].
2010 2010/06/01; 67(6):[781-7 pp.]. Available from: https://doi.org/10.1002/ana.21976.
15.
Wang Y, Lang W, Zhang Y, Ma X, Zhou C, Zhang H-L. Long-term prognosis of Guillain-Barré
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19.
Bernsen RA, Jacobs HM, de Jager AE, van der Meché FG. Residual health status after Guillain-
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20.
Bernsen RAJAM, de Jager AEJ, Schmitz PIM, van der Meché FGA. Residual physical outcome
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21.
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and private life after Guillain–Barré syndrome. Journal of the Neurological Sciences [Internet]. 2002
2002/09/15/; 201(1):[13-7 pp.]. Available from:
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22.
Fletcher DD, Lawn ND, Wolter TD, Wijdicks EFM. Long-term outcome in patients with
Guillain–Barré syndrome requiring mechanical ventilation. Neurology [Internet]. 2000; 54(12):[2311
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23.
Martic V, Bozovic I, Berisavac I, Basta I, Peric S, Babic M, et al. Three-Year Follow-Up Study in
Patients with Guillain-Barré Syndrome. Canadian Journal of Neurological Sciences / Journal Canadien
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syndrome/F9B56E8172040A3A0D8E79DB9B4D9902.
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